Practitioners of alternative medicine recommend curcumin, a component of the spice turmeric, as a treatment for autoimmune diseases. Scleroderma is a debilitating autoimmune disease that affects over 100,000 people in the US, mostly women. The hallmark of scleroderma is dermal fibrosis. When accompanied by visceral organ fibrosis, significant morbidity and mortality results. Despite its widespread occurrence, little is known to suggest effective treatment. As part of our long-term objective of understanding the aberrant regulation of extracellular matrix protein accumulation in scleroderma, we treated primary fibroblast cultures from the lungs of scleroderma patients with curcumin. We found that this treatment inhibits collagen accumulation and promotes cell death in these cultures while having no effect on normal lung fibroblasts. Interestingly, these effects of curcumin on scleroderma fibroblasts are enhanced in the presence of vitamin C. If curcumin were to have the same effect on scleroderma fibroblasts in vivo as it has in culture, then curcumin would be likely to be an effective treatment for scleroderma. While curcumin is not yet used in standard medical practice, in Chinese and Indian folk medicine turmeric is used to treat a broad range of ailments. Published articles show curcumin to have a range of potent biological activities including anticancer, anti-inflammatory, and antimicrobial. The use of curcumin in folk medicine, published studies on curcumin, and our results combine to indicate that curcumin is non-toxic and is a treatment already used in alternative medicine that is likely to have demonstrably positive effects on patients with scleroderma and other fibrotic diseases. In order to test the hypothesis that curcumin may be a beneficial treatment for scleroderma in particular and fibrotic diseases in general, we will: 1) Use cultured fibroblasts to determine the molecular and cellular mechanisms involved in the specific effects of curcumin on cells from scleroderma patients and 2) We will perform translational research using an animal model for scleroderma and lung fibrosis to determine whether curcumin is indeed effective in treating lung fibrosis in vivo. These experiments will demonstrate the efficacy and the scientific basis for that efficacy of a disease treatment already recommended by practitioners of alternative medicine.